Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy

Vitamin D deficiency has been reported in patients with chronic inflammatory conditions, such as rheumatic and inflammatory bowel diseases (IBD). We evaluated the role of biologic therapy on vitamin D, calcium and parathormone (PTH) levels. This cross-sectional study enrolled consecutive patients with either rheumatic diseases or IBD who underwent an ambulatory visit. Patients receiving vitamin D/calcium supplementation were excluded. Vitamin D deficiency or insufficiency was diagnosed when values were <20 ng/mL and 21–29 ng/ml, respectively. Patients were sub-grouped according to biologic therapy. A multivariate analysis was performed. Two-hundred patients, including 136 with a rheumatic disease (M/F 37/99; mean age 60.7 ± 12.9 years) and 64 with IBD (M/F 41/23; Mean age 49.6 ± 13.1 years) were enrolled. Vitamin D deficiency/insufficiency was detected in as many as 63.5 % patients, being 61.8 and 67.2 % in patients with either rheumatic diseases or IBD, respectively. The prevalence of vitamin D deficiency/insufficiency was higher in those receiving biologics than other therapies (78.3 vs 43.2 %; p < 0.0001), in either rheumatic diseases (78.7 vs 41 %; p < 0.0001) or IBD (75 vs 50 %; p = 0.03) group. At multivariate analysis, only biologic therapy was independently associated with vitamin D deficit (OR 4.61; p = 0.001). Patients with vitamin D deficiency/insufficiency had hypocalcemia more frequently than controls (22.8 vs 10.9 %; p = 0.03), while PTH values did not differ significantly. This study finds that the prevalence of vitamin D deficiency/insufficiency was very high in patients with either rheumatic diseases or IBD receiving a biologic therapy.     

Prevalence and predictors of vitamin D insufficiency in supplemented and non-supplemented women with systemic lupus erythematosus in the Mediterranean region

It has been previously reported that vitamin D deficiency is more prevalent among SLE patients than in the general population. We sought to determine the prevalence of vitamin D insufficiency and deficiency and their related factors, its relationship to SLE symptoms and disease activity on a group of supplemented and non-supplemented female SLE patients from the Mediterranean region. We performed a cross-sectional study including female SLE patients who regularly attended the outpatient Lupus Unit at Parc de Salut Mar-IMAS in Barcelona, from January 2012 to May 2014. Collected data were sociodemographics, vitamin D supplementation, fatigue degree visual analog scale, pharmacological treatment, main SLE serological markers, indexes, scales and plasma levels of 25-hydroxyvitamin D. One hundred and two consecutive female SLE patients were included. Vitamin D overall insufficiency and deficiency were exhibited by 46 and 22.5 % of patients, respectively. Vitamin D insufficiency was found in 50 % of supplemented and 60 % of non-supplemented patients. Among non-supplemented female SLE patients, it was found that patients with vitamin D insufficiency showed more fatigue (p = 0.009) and received more oral corticosteroids (p = 0.02) than those with normal levels. Patients with vitamin D insufficiency (supplemented and non-supplemented) received more oral corticosteroids than those without insufficiency (p = 0.008). Vitamin D insufficiency is highly prevalent among female SLE patients, even in southern regions. Non-supplemented female SLE patients showed more fatigue and received more oral corticosteroids than those with normal levels of vitamin D. These data were not found in supplemented patients although having a high prevalence of vitamin D insufficiency (up to 50 %). Further studies with longer follow-up and larger population are needed to confirm our observations.     

Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature

Hypovitaminosis D is increasingly reported in autoimmune diseases. We investigated the 25-OH-vitamin D (25-OH-vitD) levels in systemic sclerosis (SSc) patients, in correlation with disease’s features. We measured the 25-OH-vitD serum levels in 140 consecutive patients (F/M 126/15; mean age 61 ± 15.1 years), 91 without (group A) and 49 with (group B) 25-OH-cholecalciferol supplementation. Patients of group A invariably showed low 25-OH-vitD levels (9.8 ± 4.1 ng/ml vs. 26 ± 8.1 ng/ml of group B); in particular, 88/91 (97%) patients showed vitamin D deficiency (<20 ng/ml), with very low vitamin D levels (<10 ng/ml) in 40 (44%) subjects. Only 15/49 (30.6%) patients of group B reached normal levels of 25-OH-vitD (≥30 ng/ml), whereas vitamin D deficiency persisted in 12/49 (24.5%) individuals. Parathormone levels inversely correlated with 25-OH-vitD (r = ?0.3, p < 0.0001). Of interest, hypovitaminosis D was statistically associated with autoimmune thyroiditis (p = 0.008), while calcinosis was more frequently observed in patients of group A (p = 0.057). Moreover, we found significantly higher percentage of serum anticentromere antibodies in group B patients with 25-OH-vitD level ≥30 ng/ml (8/15 vs. 6/34; p = 0.017). In literature, hypovitaminosis D is very frequent in SSc patients. An association with disease duration, calcinosis, or severity of pulmonary involvement was occasionally recognized. Hypovitaminosis D is very frequent in SSc and severe in a relevant percentage of patients; furthermore, less than one third of supplemented subjects reached normal levels of 25-OH-vitD. The evaluation of 25-OH-vitD levels should be included in the routine clinical work-up of SSc. The above findings expand previous observations and may stimulate further investigations.     

Vitamin D deficiency as a risk factor for the development of autoantibodies in patients with ASIA and silicone breast implants: a cohort study and review of the literature

The development of autoimmunity and/or autoimmune diseases is multifactorial. Vitamin D is one of the factors that might play a role. We postulated that both the presence of adjuvants and insufficient levels of vitamin D may result in the development of autoimmunity in patients with autoimmune/inflammatory syndrome induced by adjuvants (ASIA) in relation to silicone implant incompatibility. We measured vitamin D levels in 135 patients with ASIA in relation to silicone implant incompatibility and related findings to the presence of autoantibodies that are commonly used to diagnose systemic autoimmune diseases. Furthermore, we systematically reviewed the literature regarding vitamin D deficiency as a risk factor for the development of autoantibodies. Vitamin D measurements were available for analysis in 131 of 135 patients with ASIA in relation to SIIS. Twenty-three patients (18%) tested positive for autoantibodies, from which 18 patients (78%) had either a vitamin D deficiency or insufficiency (median vitamin D level 60.5 mmol/L), whereas five patients (22%) had sufficient vitamin D levels. The risk to develop autoantibodies was significantly increased in vitamin D deficient and/or insufficient patients [RR 3.14; 95% CI, 1.24–7.95; p = 0.009]. Reviewed literature suggested an association between vitamin D levels and the presence and/or titer levels of autoantibodies in different autoimmune diseases. From our current study and from our review of the literature, we conclude that vitamin D deficiency is related to the presence of autoantibodies. Whether vitamin D supplementation results in a decrease of autoimmunity needs to be studied prospectively.     

Does the presence of secondary antiphospholipid syndrome in patients with systemic lupus erythematodes accelerate carotid arteries intima-media thickness changes?

Patients with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. The aim of our study was to evaluate the importance of secondary antiphospholipid presence (SAPS) in light of carotid artery intima-media thickness (CIMT) changes in SLE patients. Our study included 120 patients with SLE (46.02 ± 13.16 years), 108 women and 12 men divided into two groups: 58 patients with SAPS and 62 SLE patients without SAPS taken as a control group. All patients underwent assessment of CIMT of right and left common carotid artery (CCA) and left and right internal carotid artery (ICA) by Doppler ultrasonography. In SAPS group, 48.3 % patients had significant changes of carotid arteries comparing to 16.1 % patients in control group (p = 0.008). Average CIMT values in left and right CCA and right ICA were significantly higher in SAPS group. No significant relationship between antiphospholipid antibody type and CIMT changes was established. Multivariate regression analysis revealed SAPS as a significant predictor of CIMT changes in SLE patients (p = 0.025). Presence of SAPS in SLE patients is associated with significant CIMT changes. Additional autoimmune burden leads to a need for a more aggressive education and prevention considering standard risk factors in this group of patients.     

The predictive factors of low serum 25-hydroxyvitamin D and vitamin D deficiency in patients with systemic lupus erythematosus

Vitamin D is a steroid hormone with pleiotropic effects. The association between serum 25-hydroxyvitamin D level [25(OH) D] and lupus nephritis are not clearly known. We aim to determine serum 25(OH) D levels in patients with inactive SLE, active SLE without lupus nephritis (LN) and active SLE with LN and to identify clinical predictor of vitamin D deficiency. One hundred and eight SLE patients were included. Patients were classified as Group (Gr) 1, 2 and 3 if they had SLE disease activity index (SLEDAI) <3, ≥3 but no LN and ≥3 with LN. Important baseline characteristics were collected. 25(OH) D was measured by high performance liquid chromatography (HPLC). SLEDAI in Gr1, Gr2 and Gr3 was 0.7 (0.9), 5.6 (2.3) and 9.2 (5.2), respectively. 43.5 % had vitamin D insufficiency and 29.6 % had vitamin D deficiency. Mean 25(OH) D in each groups was 28.3 (8.0), 26.7 (9.5) and 19.9 (7.6) ng/ml (p < 0.001 comparing Gr1 and 3) (p = 0.003 comparing Gr2 and 3). Vitamin D deficiency was found in 11.1, 22.2 and 55.6 % of Gr1, 2 and 3. Linear regression analysis found that 25(OH) D was significantly correlated with serum albumin (r = 0.28, p = 0.004), inversely correlated with SLEDAI (r = ?0.22, p = 0.03) and urinary protein creatinine index (UPCI) (r = ?0.28, p = 0.005), but not with sun exposure score, body mass index and estimated GFR. Only UPCI was significantly inversely correlated with 25(OH) D (p = 0.02) from multiple linear regression. LN was a significant predictor of vitamin D deficiency from multivariate logistic regression (OR 5.97; p = 0.006). Vitamin D deficiency and insufficiency was found in 93 and 86 % of LN with proteinuria ≥ and <500 mg/day. We conclude that SLE patients with LN have significantly lower vitamin D level than inactive SLE and active SLE without LN. Hence, nephritis is a significant predictor of vitamin D deficiency in SLE patients.     

Vitamin D Deficiency Is Associated with Ulcerative Colitis Disease Activity

Purpose

Previous studies on experimental mouse models have suggested a role of vitamin D in immune system regulation and IBD disease severity. In this study, we examine the relationship between vitamin D levels and clinical disease activity in human subjects with ulcerative colitis (UC). We hypothesized that patients with vitamin D deficiency will display increased UC disease activity as compared to patients with normal vitamin D levels.

Methods

A cross-sectional study was performed by querying the outpatient electronic medical record of our health system for patients seen in the gastroenterology clinic from January 2007 to October 2009 who carried both a diagnosis of UC and a documented 25-OH vitamin D level within 30 days of their clinic visit. Demographic and clinical variables were collected. Clinical disease activity was calculated using the six-point partial Mayo index. Active disease was defined as a six-point index score of ≥1. Vitamin D deficiency was defined as a 25-OH D level below 30 ng/ml. Data were analyzed using the chi-square distribution test.

Results

Thirty-four patients met inclusion criteria (53 % female, mean age 45.7 ± 24.7 years). Fifteen patients had normal vitamin D levels and 19 patients were vitamin D deficient. Twelve patients had vitamin D levels <20 ng/ml. Vitamin D deficient patients were statistically more likely to have increased disease activity than patients with normal vitamin D levels (p = 0.04), with 68 % of deficient patients displaying active disease compared with 33 % in the sufficient group. There was also a statistically significant association between vitamin D status and need for treatment with steroids, with a higher percentage of vitamin D deficient patients (47 %) requiring such treatment compared with 7 % in the sufficient group (p = 0.02). There was no association between season of visit and disease activity.

Conclusion

Vitamin D deficiency is common among patients with active UC, particularly those requiring corticosteroids. Further investigation is needed to determine the clinical utility of vitamin D monitoring in patients with UC and whether there is a role for vitamin D as a treatment for UC.     

Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross‐sectional study

Objective

An association between systemic autoimmune diseases and atherosclerosis has been described in many connective tissue diseases, and this association is known to lead to increased cardiovascular morbidity and mortality. Systemic sclerosis (SSc) is characterized by multisystem organ inflammation, endothelial wall damage, and vasculopathy. There are many markers of endothelial dysfunction and/or atherosclerotic risk, such as asymmetric dimethylarginine (ADMA), arterial stiffness parameters, carotid intima‐media thickness (CIMT), and coronary flow reserve (CFR) assessed by transthoracic echocardiography. The aim of this pilot study was to use various endothelial and atherosclerosis markers to identify early cardiovascular involvement in a group of SSc patients.

Methods

The study involved 20 patients (2 men and 18 women with a mean ± SD age of 52.96 ± 12.51 years) with diffuse SSc who had no signs or symptoms of cardiovascular disease (CVD) and 20 age‐ and sex‐matched controls. All subjects underwent a dipyridamole echocardiographic stress test that included a determination of CFR and an evaluation of CIMT, arterial stiffness, and plasma ADMA levels.

Results

All of the arterial wall measurements of the patients with diffuse SSc were significantly different from those of the controls, and both right and left CIMT, pulse wave velocity, and stiffness index (β) were significantly elevated in the SSc patients compared to the healthy controls. Moreover, in patients with diffuse SSc, CFR was significantly lower (P = 0.0033) and plasma ADMA levels were higher (P < 0.0001) than in healthy controls.

Conclusion

SSc patients without any clinical evidence of CVD seem to have had subclinical atherosclerosis, which was suggested by early impairment of coronary microcirculation and macrovascular involvement.     

Vitamin D Deficiency and Its Association with Inflammatory Markers,Lipid Profile and Regulatory T-cells in Pediatric Sickle Cell Disease Patients

We investigated vitamin D deficiency in pediatric sickle cell disease patients and its association with selected bone, lipid and inflammatory parameters. The study included 64 patients (33 SS and 31 SB) and 21 carriers (AS). Blood was obtained to assess levels of vitamin D, WBC, CRP, Ca, P, ALP, PTH, triglyceride, total cholesterol, LDL, VLDL, HDL, IL-2, IL-12, TNF-α, IL-4, IL-6, IL-10 and regulatory T cells. The patients were grouped according to their genotype (SS, SB) and vitamin D status (low or normal). Carriers were also grouped as low or normal vitamin D. Laboratory findings were similar between low and normal Vit D groups in SS, SB and AS genotypes except a lower IL-12 in SB-low vitamin D compared SB-normal vitamin D group. Acute chest syndrome was more frequent in SS-low Vit D (63%) compared to SS-normal Vit D (25%), SB-low Vit D (21%) and SB-normal Vit D (33%) (P = 0.045). Both SS and SB with low vitamin D had higher VLDL (P = 0.006 and P = 0.022), TNF-α (P = 0.001) and regulatory T cells (P = 0.000) compared to AS-low vitamin D. Both SS and SB with normal vitamin D had higher levels of regulatory T cells (P = 0.000) compared to AS-normal vitamin D. Vit D was not a modifier of selected inflammation, bone and lipid parameters in sickle cell disease. Acute chest syndrome was comparably more frequent in SS-low vitamin D. Increase of regulatory T cells in the patients was a result of chronic inflammation in sickle cell disease.     

Vitamin D Receptor (VDR) Gene Polymorphisms (<Emphasis Type="Italic">Fok</Emphasis>I, <Emphasis Type="Italic">Bsm</Emphasis>I) and their Relation to Vitamin D Status in Pediatrics βeta Thalassemia Major

Vitamin D is critical for calcium, phosphate homeostasis and for mineralization of the skeleton, especially during periods of rapid growth. Vitamin D Deficiency leads to rickets (in children) and osteomalacia (in adults). Expression and activation of the vitamin D receptor (VDR) are necessary for the effects of vitamin D, in which several single nucleotide polymorphisms have been identified especially (FokI, BsmI). In this study serum 25 (OH) vitamin D3 levels were estimated by Enzyme Linked Immunosorbent Assay [ELISA], VDR (FokI, BsmI) gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay [PCR–RFLP].Serum levels of calcium, phosphorus, alkaline phosphatase and ferritin were determined in 50 Pediatrics beta thalassemia major patients and 60 controls. Patients had significantly lower serum calcium (p < 0.001) lower serum vitamin D3 (p < 0.001) with elevated levels of phosphorus (p < 0.001) and alkaline phosphatase than controls (p = 0.04). Of the patients studied, 60 % had vitamin D deficiency (<20 ng/ml), 20 % had vitamin D insufficiency (21–30 ng/ml) and 20 % had sufficient vitamin D status (>30 ng/ml). Patients harboring mutant (Ff,ff) and wild (BB) genotypes were associated with lower serum calcium (p = 0.08, 0.02) respectively, lower vitamin D3 levels (p < 0.001, 0.01) respectively. They were also suffering from more bony complications although the difference was not statistically significant (p > 0.05). In conclusion, these results suggest that the VDR (FokI, BsmI) gene polymorphisms influence vitamin D status, (Ff,ff), BB genotypes had lower vitamin D levels, so they might influence risk of development of bone diseases in beta thalassemia major.     

Relationship of serum osteoprotegerin with arterial stiffness,preclinical atherosclerosis,and disease activity in patients with ankylosing spondylitis

Patients with ankylosing spondylitis (AS) reportedly have a higher mortality and morbidity risk. Osteoprotegerin (OPG) was recently defined as an important cardiovascular (CV) marker in the general population. We aimed to assess the relationship of serum OPG levels with arterial stiffness, carotid intima media thickness (CIMT), and clinical and laboratory data in AS patients. We examined 60 AS patients without CV disease or risk factors and 50 healthy controls. Disease activity was evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS), whereas functional capacity was evaluated using the Bath Ankylosing Spondylitis Functional Index (BASFI). Serum OPG levels were measured with the enzyme-linked immunosorbent assay. Carotid-femoral pulse wave velocity (PWV) was used as an indicator of arterial stiffness, whereas CIMT (examined via carotid ultrasonography) was used to evaluate preclinical atherosclerosis. The mean serum OPG level, PWV, and CIMT were significantly higher in AS patients than in controls (106.7?±?50.9 vs. 58.1?±?12.7 pg/mL; 7.4?±?1.8 vs. 6.2?±?1.2 m/s; 0.72?±?0.13 vs. 0.57?±?0.07 mm, respectively; P?<?0.001 for all). In AS patients, the serum OPG levels were not significantly correlated with PWV and CIMT but were significantly correlated with erthrocyte sedimentation rate, BASFI, and ASDAS. AS patients without CV disease or risk exhibited high OPG levels and increased PWV and CIMT values. Although OPG levels were not significantly correlated with PWV or CIMT, future long-term follow-up studies will help define the predictive value of OPG in these patients.     

Increased plasma miR-146a levels are associated with subclinical atherosclerosis in newly diagnosed type 2 diabetes mellitus

AimsThe association between circulating miR-146a and subclinical atherosclerosis in type 2 diabetes mellitus (T2DM) remains poorly understood. This study aimed to investigate the correlation between plasma miR-146a levels and subclinical atherosclerosis as measured by the carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (baPWV) in patients with newly diagnosed T2DM.MethodsWe studied 100 patients with newly diagnosed T2DM. Subclinical atherosclerosis was defined as a thickened CIMT (≥1.0 mm) and high baPWV defined as a value greater than the 75th percentile. Plasma miR-146a levels and metabolic parameters were measured.ResultsPatients with thickened CIMT had higher plasma miR-146a levels than those without thickened CIMT (3.36 ± 1.32 vs 1.38 ± 1.11, P < 0.001). Patients in the high baPWV group had higher plasma miR-146a levels than those in the normal baPWV group (3.43 ± 1.32 vs 1.98 ± 1.48, P < 0.001). Both CIMT (β = 0.569, P < 0.001) and baPWV (β = 0.274, P = 0.001) positively correlated with plasma miR-146a levels after adjustment for confounding factors by multiple stepwise regression. On binary logistic regression, plasma miR-146a level was an independent risk factor for thickened CIMT (OR = 3.890, 95% CI 1.415–7.698, P = 0.008) and high baPWV (OR = 1.954, 95% CI 1.256–3.040, P = 0.002) after adjustment for established cardiovascular risk factors. The area under the receiver operating characteristics curve (AUROC) of plasma miR-146a level for predicting thickened CIMT was 0.795 (95%CI 0.708–0.883, P < 0.001) and for predicting high baPWV was 0.773 (95%CI 0.679–0.867, P < 0.001).ConclusionPlasma miR-146a levels correlate with CIMT and baPWV and could act as a biomarker for early diagnosis and as a therapeutic target for atherosclerosis in T2DM.     

Serum osteoprotegerin concentration is associated with carotid atherosclerotic plaque in patients with rheumatoid arthritis

Objective

Osteoprotegerin (OPG), a regulator of bone resorption, is involved in the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. OPG is elevated in patients with coronary artery disease, and high OPG levels are associated with cardiac disease severity and mortality in the general population. The purpose of this study was to investigate the relationship of serum OPG levels, traditional coronary risk factors, and RA-related factors to carotid atherosclerosis in RA patients.

Methods

Ninety-one RA patients were studied (85 % women, age 60 ± 10 years). Serum OPG levels were measured by an enzyme-linked immunosorbent assay. The prevalence of carotid plaque was assessed by ultrasonographic imaging in all patients. The relationship between various clinical characteristics, OPG, and carotid plaque was examined.

Results

Serum OPG levels were significantly higher in patients with carotid plaque than in those without plaque (median level 1,397 vs. 887 pg/mL, respectively; P = 0.006). There were no significant differences between RA patients with and without carotid plaque with respect to sex, duration of RA, blood pressure, body mass index, smoking, low-density lipoprotein cholesterol, Disease Activity Score-28, van der Heijde-modified Sharp score, and prednisolone dose. After adjusting for age, sex, and C-reactive protein, elevated levels of OPG were still associated with a higher prevalence of carotid plaque in patients with RA (P = 0.038).

Conclusion

RA patients suffer from accelerated atherosclerosis and also have increased levels of OPG. The serum OPG level is independently associated with carotid plaque.     

Brachial-ankle pulse wave velocity is an independent predictor of carotid artery atherosclerosis in the elderly

Objective Brachial-ankle pulse wave velocity （baPWV） is widely used as a simple noninvasive measure of arterial softness. The aim of this study was to evaluate the usefulness of baPWV as a predictor of the carotid artery atherosclerosis in the elderly. Methods A total of 721 elderly participants （mean ~ SD age, 70.3 -4- 5.6years） were enrolled in the current study. All participant underwent both baPWV measurement and B-mode ultrasound for the intima-media thickness. Carotid atherosclerosis （CAS） was defined as the present of carotid plaque or and/or intima media thickness for at least 1.1 mm. Results A multivariate logistic regression analysis reveals that age, sex, brachial-ankle pulse wave velocity, smoking and LDL-C level showed a significant correlation with the presence of CAS. The odds ratios of CAS associated with a 500cm/s increase of brachial-ankle pulse wave velocity were 2.378 [95% confidence interval, 1.36 to 4.00, P〈0.05], 3.733 [95% confidence interval, 1.729 to 8.058, P〈0.01], 4.438 [95% confidence interval, 1.659 to 11.803, P〈0.01]. The baPWV significantly correlated with IMT by bivariate correlation analysis （r=-0.39; p=0.001）. After adjusting for factors influencing, baPWV all the same correlated with IMT （r=-0.35; p=0.001）.Conclusion These results indicate that brachial-ankle PWV is an independent predictor of CAS in the elderly.It also means that the direct measurement of arterial stiffness by this simple method may be of great help for the evaluation of carotid artherosclerosis, at least in the elderly     

Effect of vitamin D supplementation on reduction of cardiometabolic risk in patients with type 2 diabetes mellitus and dyslipidemia

Endothelial progenitor cells (EPCs) participate in endothelial regeneration. Previous studies link vitamin D deficiency, inflammatory cytokines, and cardiovascular disease (CVD) risk. This study evaluates the impact of vitamin D supplementation on EPCs, inflammatory markers, and glycemia in type 2 diabetes. This is prospective open-label randomized controlled study. Sixty-five patients with type 2 diabetes, dyslipidemia, HbA_1c below 9%, and vitamin D deficiency (below 30 ng/ml) attending the outpatient clinic between April and December 2015 were randomized to active vitamin D (60,000 IU of vitamin D orally once a week for 8 weeks, followed by once a month for 4 months) or control for 6 months. Data was analyzed with STATA 14. Demographics include median age 54 (range 48.5–60) years, median duration of diabetes 7 (4–12.5) years, mean BMI 26.86 ± 3.8 kg/m², mean HbA_1c 7.22±0.8%, and median vitamin D 13.42 (range 10.24–17.23) ng/ml; 50% were men. Vitamin D supplementation increased vitamin D levels in the active group compared to control (p < 0.01). EPCs decreased in both groups from baseline. There was no difference in change in EPCs, hsCRP, IL-6, IL-10, TNF-α, and HbA_1c or insulin resistance (HOMA-IR) between the active- and control-groups at the end of the study. Vitamin D supplementation did not alter EPCs or inflammatory markers, or improve glycemic control at the dose and duration investigated. Further studies are needed to study the long-term effects on markers of endothelial repair.     

Very low levels of vitamin D in systemic sclerosis patients

Vitamin D displays many extraosseous immunomodulatory effects. The aim of the study was to evaluate the level of vitamin D in patients with systemic sclerosis (SSc) and to analyze the associations between the concentration of the vitamin and clinical manifestations. In March-April 2009, 65 consecutive SSc patients underwent evaluation of vitamin D concentrations by the LIAISON immunoassay (normal 30-100 ng/ml). Serum levels between 10 and 30 ng/ml were classified as vitamin D insufficiency, while concentrations <10 ng/ml as vitamin D deficiency. None of the patients were receiving vitamin D supplementation at the time of or during the year prior to study entry. The mean level of vitamin D was 15.8 ± 9.1 ng/ml. Only three cases showed normal values; vitamin D insufficiency and deficiency were found in 43 and 19 cases, respectively. Patients with vitamin D deficiency showed longer disease duration (13.1 ± 6.8 versus 9.4 ± 5.5 years, P = 0.026), lower diffusing lung capacity for carbon monoxide (63.7 ± 12.4 versus 76.4 ± 20.2, P = 0.014), higher estimated pulmonary artery pressure (28.9 ± 9.9 versus 22.8 ± 10.4, P = 0.037) and higher values of ESR (40 ± 25 versus 23 ± 13 mm/h, P = 0.001) and of CRP (7 ± 7 and 4 ± 2 mg/l, P = 0.004) in comparison with patients with vitamin D insufficiency; moreover, late nailfold videocapillaroscopic pattern was more frequently found (52.6% versus 18.6%, P = 0.013). None of the patients showed evidence of overt mal-absorption. Low levels of vitamin D are very frequent in patients with SSc. Intestinal involvement is not likely the cause of vitamin D deficit; other factors such as skin hyperpigmentation and reduced sun exposition for psychological and social reasons may be implicated. Patients with vitamin D deficiency showed more severe disease in comparison with patients with vitamin D insufficiency, above all concerning lung involvement. Further trials are awaited to determine whether vitamin D could represent a modifiable factor able to interfere with SSc evolution.     

Vitamin D deficiency and the associated factors in children with type 1 diabetes mellitus in southern Iran

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder caused by destruction of beta cells of the pancreas. Several reports have suggested a connection between vitamin D deficiency and T1DM and the possible role of dietary vitamin D supplementation in reducing the risk of T1DM. There is little knowledge about the prevalence of vitamin D deficiency among Iranian children with T1DM. Serum 25-hydroxy vitamin D (25OHD) was assayed by high performance liquid chromatography in 8–18-year-old diabetic patients referred to pediatric diabetes clinics in Shiraz, Iran, during a period of 14 months. The age of the onset of T1DM, daily insulin usage, weight, height, and BMI of each patient were recorded along with levels of physical activity and sun exposure. The patients’ body composition was determined by DEXA and used in further analysis. This study was conducted on 39 diabetic boys and 46 diabetic girls aged 12.4 ± 4.2 years. Mean serum 25(OH)D3 was 18 ± 12.2 ng/dl. Serum levels of 25(OH)D3 were higher in boys than girls. 7.7 % of the boys and 30.4 % of the girls had severe vitamin D deficiency. There was a negative correlation between the age of the onset of T1DM and serum concentration of 25(OH)D3 (p = 0.006, r = ?0.17). Girls with T1DM showed a higher prevalence of severe vitamin D deficiency than boys with T1DM. Moreover, vitamin D deficiency was more prevalent in individuals with earlier onset of the disease and in those with higher fat mass index.     

Low serum fibroblast growth factor 2 levels not accompanied by increased serum pentraxin 3 levels in patients with systemic sclerosis

There are scarce clinical data regarding serum pentraxin 3 (PTX3) and fibroblast growth factor 2 (FGF2) in patients with systemic sclerosis (SSc). Study was conducted to evaluate serum levels in our SSc cohort. Serum PTX3 and FGF2 concentrations were compared among SSc, disease control (systemic lupus erythematosus (SLE)), and healthy control groups. We also examined the association of serum levels of PTX3 and FGF2 with disease manifestations. Serum PTX3 levels were similarly distributed among SSc (n = 93) and healthy groups (n = 66) (p = 1.00) while PTX3 levels were higher in SLE controls (n = 86) compared to both SSc and healthy groups. PTX3 levels were higher in limited SSc cases compared to diffuse cases (p = 0.016). Median PTX3 levels in SSc cases with lung involvement were lower compared to cases with no lung involvement (p = 0.006). Patients with SSc had significantly lower serum levels of FGF2 compared to SLE and healthy groups. Serum FGF2 concentration was undetectable in 61.3% of cases with SSc while 30.2% of SLE and only 4.5% of healthy cases had undetectable FGF2 levels (p < 0.01). Diffuse and limited SSc cases, as well as cases with and without lung involvement, had similar rates of undetectable serum FGF2 levels (p = 0.15 and p = 0.59, respectively). FGF2 levels were mostly undetectably low in patients with SSc, and serum PTX3 was lower in diffuse SSc and in cases with lung involvement compared to limited SSc and cases with no lung involvement, respectively, in our cohort.     

Increased Pulse Wave Velocity and Carotid Intima-Media Thickness in Patients with Ulcerative Colitis

Background

Ulcerative colitis (UC) is characterized with chronic, progressive inflammation of the gastrointestinal tract. The association of UC with cardiovascular disease is still a matter of debate.

Aim

The aim of this study was to investigate whether carotid intima-media thickness (CIMT) and carotid-femoral pulse wave velocity (cf-PWV) as surrogates of atherosclerosis and arterial stiffness are increased in patients with UC.

Methods

Our study was cross-sectional and observational in design. Baseline characteristics were recorded during interview with the patient. Patients with previous cardiovascular disease, rheumatoid arthritis, chronic renal failure, and infectious and inflammatory disorders other than UC were excluded. Thirty-seven consecutive patients with UC and 30 control participants underwent cf-PWV assessment and CIMT measurement. The diagnosis of UC was based on clinical, radiologic, endoscopic, and histological findings.

Results

CIMT, cf-PWV, and C reactive protein were significantly higher in patients with UC. Although linear regression analyses identified UC as an independent predictor of CIMT (β ± SE, 0.39 ± 0.08; p < 0.001), only age independently predicted cf-PWV (β ± SE, 0.08 ± 0.03; p = 0.003) in our study population. Moreover, we revealed higher CIMT and PWV values in patients with higher disease activity and more extensive involvement, compared to patients with mild activity and limited disease.

Conclusion

We revealed increased pulse wave velocity and CIMT in patients with UC. UC appears to be associated with arterial stiffness and atherosclerotic burden, but the underlying mechanisms require further studies to be identified.